Metrohm QTRam Portable Raman spectrometer

Importance of the topic

In pharmaceutical manufacturing and quality control, ensuring uniform content of the active pharmaceutical ingredient (API) in solid dosage forms is critical for patient safety and regulatory compliance. Transmission Raman spectroscopy offers a rapid, nondestructive approach to quantify API concentration, polymorphic forms and crystallinity without sample preparation or consumables. Its portability enables at-line measurements, supporting real-time release testing and process analytical technology (PAT) initiatives.

Objectives and study overview

The primary goal of this application note is to demonstrate how the QTRam® portable transmission Raman spectrometer implements STRaman® technology for content uniformity testing of tablets, capsules and gels. It also highlights additional applications—such as formulation development under Quality by Design (QbD) frameworks and counterfeit detection—while outlining software-driven workflows for rapid quantitative analysis and reporting.

Methodology and used instrumentation

This study employs the QTRam® system powered by B&W Tek’s STRaman® technology, featuring:

• 785 nm laser source with >420 mW adjustable power at the sample
• Transmission Raman optical layout for high-throughput analysis of large sample volumes
• QT-Sampler® and custom sample holders accommodating diverse tablet and capsule geometries
• Integrated BWAnalyst® touchscreen software (21 CFR Part 11 compliant) for data acquisition, method development, quantitative predictions, report configuration, electronic signatures and audit trails
• BWIQ® chemometric software for multivariate calibration model generation

Measurements require no sample preparation, consumables or waste disposal. Results are delivered within seconds on the built-in tablet computer.

Main results and discussion

Using transmission Raman spectra, the QTRam® system achieved:

• Accurate quantification of one or multiple APIs and excipients in solid dosage forms
• Assessment of crystallinity and polymorphic composition from a single measurement
• Rapid method development via step-by-step quantitative modeling embedded in the software

Data demonstrate excellent correlation between predicted and reference concentrations, meeting USP <905> content uniformity requirements. The absence of sample handling reduces variability and accelerates workflow.

Benefits and practical applications of the method

The QTRam® portable spectrometer offers multiple advantages in pharmaceutical environments:

• At-line capability for real-time quality control in manufacturing lines
• Validation-friendly software fulfilling 21 CFR Part 11 regulations
• Non-destructive testing that preserves sample integrity for further analysis
• Elimination of sample prep and consumables, lowering operational costs
• Versatility for formulation optimization, PAT strategies and counterfeit screening

Future trends and potential uses

Emerging directions for transmission Raman spectroscopy include:

• Integration with continuous manufacturing platforms for inline monitoring
• Advanced chemometric algorithms (machine learning, deep learning) to enhance predictive accuracy
• Miniaturization and wireless connectivity for decentralized quality control
• Expansion into biologics (liposomal formulations, solid-state proteins) and complex drug-device combinations

Conclusion

The QTRam® system, built on STRaman® technology, provides a powerful tool for rapid, nondestructive quantitative analysis of solid dosage forms. Its portable design, robust software suite and absence of consumables position it as a versatile solution for content uniformity testing, formulation development, counterfeit detection and broader PAT implementations.

Reference

• B&W Tek, LLC. Doc-Rev: 280001286-E (2020/03/31).